Amantadine's Neuroprotective Effects in Rabbit Spinal Cord Ischemia/Reperfusion Model.

Abstract

To examine the effects of amantadine, a drug with neuroprotective and anti-inflammatory activities on oxidative stress, tissue necrosis, apoptosis, and neurological recovery in an experimental rabbit spinal cord ischemia-reperfusion injury (SCIRI) model. A total of 32 rabbits were randomized into five groups: control, ischemia, vehicle, methylprednisolone (MP), and amantadine (AMT) (n=8/each). At 24th-hour neurological examination was performed, spinal cord tissues were collected, and biochemical and histopathological examinations were performed. When ischemia and vehicle groups were compared with control group, significant increase was seen in serum and tissue caspase-3, malondialdehyde (MDA), and myeloperoxidase (MPO) levels (p < 0.001); significant decrease was seen in serum and tissue catalase (CAT) levels (p < 0.001); and significant increase was seen in serum xanthine oxidase (XO) levels (p < 0.001). When the ischemia group and the MP and AMT groups were compared, low serum and tissue caspase-3 levels (p < 0.001), high serum and tissue CAT levels (p < 0.001), significantly low serum XO levels (p < 0.001), low serum and tissue MDA levels (p < 0.05) and tissue MPO levels (p < 0.001) were found. Both AMT and MP groups showed decreased histopathological score and higher number of normal neurons (p < 0.001) compared to ischemia group. Both AMT and MP showed better modified Tarlov scores compared to the ischemia group (p < 0.001). Our study found that AMT had antioxidant, anti-inflammatory, anti-apoptotic, and neuroprotective effects on SCIRI. We used biochemical, microscopic, and ultrastructural approaches to demonstrate these effects. AMT might be a candidate medication for SCIRI prophylaxis and treatment.